Comparison of Efficacy Between Combination of Amitriptyline-propranolol and Pizotifen for Migraine Prophylaxis.

Comparison of Efficacy Between Combination of Amitriptyline-propranolol and Pizotifen for Migraine Prophylaxis: A Single-blind Randomized Controlled Trial

The goal of this clinical trial is to compare efficacy and observe common adverse effects of a combination of amitriptyline-propranolol and pizotifen as prophylactic treatments for migraine. The main question it aims to answer is:

• Does pizotifen more effective than the combination of amitriptyline-propranolol in migraine prophylaxis?

Participants will be asked to :

• Maintain the provided headache diary accordingly
• Take supplied drugs as described during clinical visits
• Contact principle investigator if there is any issues regarding drug use and/or their adverse effects

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Amitriptyline-propranolol; Drug: Pizotifen

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1200
    • Bangabandhu Sheikh Mujib Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Patient of migraine (with typical aura or without aura) according to ICHD-3 (International Classification of Headache Disorder, 3rd edition) criteria.
2. Age at entry: 18 to 50 years (to minimize the risks related to adverse effects of study drugs such as drowsiness, weight gain, A-V conduction block, postural hypotension)
3. Patients not on any prophylactic medications.
4. Patients willing to take part in the study.
5. Patients being able to fill a headache diary successfully & reliably.

Exclusion Criteria:

1. Age <18 years or >50 years
2. Patients having headache other than migraine, complicated migraine, ophthalmoplegic migraine, catamenial migraine, basilar migraine.
3. Patients on prophylactic medication.
4. Co-morbidities such as heart failure, hepatic or renal impairment, diabetes, bronchial asthma, malignancy, intracranial vascular aneurysm, pregnancy & breastfeeding etc.
5. Patients having known hypersensitivity to amitriptyline, propranolol or pizotifen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amitriptyline-Propranolol; Combination of amitriptyline and propranolol. Initial 2 weeks: Amitriptyline 10 mg at bedtime Propranolol 20mg twice daily Next 2 weeks: Amitriptyline 25 mg at bedtime Propranolol 20mg three times daily Next 8 weeks: Amitriptyline 25 mg at bedtime Propranolol 40mg twice daily	Drug: Amitriptyline-propranolol; Amitriptyline will be given at bedtime only, starting at 10 mg daily and gradually increasing to 25 mg daily. Propranolol will be started in 40 mg daily in divided doses, which gradually increases to 80 mg daily in divided doses
Experimental: Pizotifen; Pizotifen Initial 2 weeks: Pizotifen 0.5 mg at bedtime Next 2 weeks: Pizotifen 1 mg at bedtime Next 8 weeks: Pizotifen 1.5 mg at bedtime	Drug: Pizotifen; Pizotifen will be given only at night time to avoid daytime somnolence. Starting dose will be 0.5mg then gradually increased to 1.5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of headache per month	Comparison of reduction of frequency of headache attack in immediate last month with initial baseline one month without any medication. These values will be compared between two study groups	12 weeks
Duration of headache per month	Comparison of reduction of total duration of headache attack in immediate last month with initial baseline one month without any medication. These values will be compared between two study groups	12 weeks
Severity of headache	Comparison of reduction of severity of headache attack in immediate last month with initial baseline one month without any medication using visual analogue scale. The visual analogue scale is numbered from 0 to 10. 0 stands for no pain, 1-3 for mild pain, 4-6 for moderate pain and 7-9 for severe pain and 10 for very severe unbearable pain. These values will be compared between two study groups	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects of drugs	Adverse effects (e.g., somnolence, dizziness, dry mouth, weight gain, constipation, bradycardia) of study drugs will be observed	12 weeks

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Investigators: Study Chair: Kanuj Kumar, MD, professor

Publications and helpful links

General Publications

• Islam MA, Shaikh AK, AlamSkM, Sultana D, Islam MS, Rashid MM. Safety and Efficacy of Propranolol and amitriptyline combination therapy in migraine prophylaxis: A Randomized Control Trial. J NatlInstNeurosci Bangladesh, 2018;4(1): 3-7
• Israil A, Ahmed S, Rahman KM, Uddin MJ, Dey SK, Battacharjee M, Mondal G, Ali MA, Alam MN, Miah AH, Uddin MS. Efficacy of amitriptyline, pizotifen and propranolol in the prevention of migraine. Mymensingh Med J. 2013 Jan;22(1):93-100.
• Chitsaz, A., Najafi, M.R., Zangeneh, F.A., Norouzi, R. and Salari, M., 2012. Pizotifen in migraine prevention: A comparison with sodium valproate. Neurology Asia, 17(4), pp.319-324.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2023
• Primary Completion (Estimated): November 25, 2023
• Study Completion (Estimated): January 15, 2024

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Estimated): December 6, 2023

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Propranolol; Amitriptyline
• Other Study ID Numbers: 4292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: April-2024 to March 2025
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No